High-dose i.v. granisetron for the prevention of chemotherapy-induced emesis: cardiac safety and tolerability

This phase II trial assessed the cardiovascular safety and tolerability of high-dose granisetron for the treatment of nausea and vomiting in cancer patients undergoing emetogenic chemotherapy. Forty-one patients were given 30-min infusions of granisetron, 40 or 120 mug/kg i.v., as either a single dose or as split doses, at 6-h intervals. Subsequently, patients had the option of the alternative dosing regimen or to return to conventional antiemetic therapy. Patients were monitored for 24 h following the first granisetron infusion. Electrocardiogram (ECG; lead II and Holter monitoring) measurements were made during the study and blood samples for pharmacokinetic analysis were taken at regular intervals for 48 h after the start of the first granisetron infusion. During the first chemotherapy session, granisetron was administered as: (i) bolus doses of 80 mug/kg (n = 3) and 120 mug/kg (n = 19) or (ii) split doses of 2 x 40 mug/kg (n = 1) and 3 x 40 mug/kg (n = 18). Crossover therapy was administered to 22 patients, with granisetron doses of 120 mug/kg (n = 12), 2 x 40 mug/kg (n = 1) and 3 x 40 mug/kg (n = 9). We conclude that supra-therapeutic doses up to 120 mug/kg granisetron had no clinically significant effect on ECG, pulse rate or blood pressure. The treatment was well tolerated with no significant changes in biochemistry or hematological parameters. (C) 2003 Lippincott Williams Wilkins.